Combinatorial SNARE Complexes Modulate the Secretion of Cytoplasmic Granules in Human Neutrophils

Mollinedo, Faustino; Calafat, Jero; Janssen, Hans; Martı́n-Martı́n, Belén; Canchado, Javier; Nabokina, Svetlana M.; Gajate, Consuelo

doi:10.4049/jimmunol.177.5.2831

Cited by 104 publications

(108 citation statements)

References 63 publications

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“…Nevertheless, the presence of chloride fluxes in Ca 2ϩ -depleted neutrophils seems to suggest that calcium-activated Cl Ϫ conductance does not play a major role in this process. Although these data conflict with previous reports (5,91), it should be noted that our findings are consistent with other studies showing that Cl Ϫ efflux triggered by the cross-linking of ␤ 2 integrins occurs in a Ca 2ϩ -independent manner (9). Another issue regarding Cl Ϫ movements in neutrophils concerns chloride localization within the cell.…”

Section: Figure 8 Effect Of CLcontrasting

confidence: 57%

Chloride Movements in Human Neutrophils during Phagocytosis: Characterization and Relationship to Granule Release

Busetto

Trevisan

Decleva

et al. 2007

The Journal of Immunology

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Chloride ion efflux is an early event occurring after exposure of human neutrophils to several soluble agonists. Under these circumstances, a rapid and reversible fall in the high basal intracellular chloride (Cl−i) levels is observed. This event is thought to play a crucial role in the modulation of several critical neutrophil responses including activation and up-regulation of adhesion molecules, cell attachment and spreading, cytoplasmic alkalinization, and activation of the respiratory burst. At present, however, no data are available on chloride ion movements during neutrophil phagocytosis. In this study, we provide evidence that phagocytosis of Candida albicans opsonized with either whole serum, complement-derived opsonins, or purified human IgG elicits an early and long-lasting Cl− efflux accompanied by a marked, irreversible loss of Cl−i. Simultaneous assessment of Cl− efflux and phagocytosis in cytochalasin D-treated neutrophils indicated that Cl− efflux occurs without particle ingestion. These results suggest that engagement of immune receptors is sufficient to promote chloride ion movements. Several structurally unrelated chloride channel blockers inhibited phagocytosis-induced Cl− efflux as well as the release of azurophilic—but not specific—granules. It implicates that different neutrophil secretory compartments display distinct sensitivity to Cl−i modifications. Intriguingly, inhibitors of Cl− exchange inhibited cytosolic Ca2+ elevation, whereas Cl− efflux was not impaired in Ca2+-depleted neutrophils. We also show that FcγR(s)- and CR3/CR1-mediated Cl− efflux appears to be dependent on protein tyrosine phosphorylation but independent of PI3K and phospholipase C activation.

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Section: Figure 8 Effect Of CLcontrasting

confidence: 57%

Chloride Movements in Human Neutrophils during Phagocytosis: Characterization and Relationship to Granule Release

Busetto

Trevisan

Decleva

et al. 2007

The Journal of Immunology

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“…Our study demonstrates that mast cells must now be added to the list of hematopoietic cells that possess distinct secretory granule subsets, each with different cargo, different functions, and in some cases distinct SNARE proteins regulating their fusion with the plasma membrane. Neutrophils possess secondary/specific granules and gelatinase-rich tertiary granules, and exocytosis of these granules is inhibited by interfering with VAMP-2 function (18). By contrast, inhibition of VAMP-7 prevents azurophilic granule release from these cells, whereas inhibition of VAMP-2 does not affect this granule subset (18).…”

Section: Vamp-8 Is Present On Serotonin-containing Lysosome-like Secrmentioning

confidence: 99%

“…Neutrophils possess secondary/specific granules and gelatinase-rich tertiary granules, and exocytosis of these granules is inhibited by interfering with VAMP-2 function (18). By contrast, inhibition of VAMP-7 prevents azurophilic granule release from these cells, whereas inhibition of VAMP-2 does not affect this granule subset (18). However, the differential regulation of discrete secretory granules by distinct SNAREs is not universally true, because VAMP-8 regulates release of all three major secretory granule subtypes in platelets (14).…”

Section: Vamp-8 Is Present On Serotonin-containing Lysosome-like Secrmentioning

confidence: 99%

Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms

Puri

Roche

2008

Proc. Natl. Acad. Sci. U.S.A.

191

189

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Mast cells degranulate and release the contents of intracellular secretory granules in response to the cross-linking of FcRI by multivalent antigens. These granules contain a variety of biologically active inflammatory mediators; however, it is not clear whether these granules are homogenous or whether there is heterogeneity within the secretory granule population in mast cells. By using genetically altered mice lacking specific vesicleassociated SNARE membrane fusion proteins, we found that VAMP-8-deficient mast cells exhibited defects in FcRI-regulated exocytosis, whereas synaptobrevin 2-or VAMP-3-deficient mast cells did not. Surprisingly, the defect in secretion in VAMP-8-deficient mice was limited to the subpopulation of mast cell secretory granules containing serotonin and cathepsin D, whereas regulated exocytosis of secretory granules containing histamine and TNF-␣ was normal. Confocal microscopy confirmed that serotonin and histamine were present in distinct intracellular granules and that most serotonin-containing granules were VAMP-8-positive. Thus, this study demonstrates that mast cells do indeed possess distinct subsets of secretory granules and that these subsets use different SNARE isoforms for exocytosis.serotonin ͉ histamine ͉ VAMP-8

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“…In a variety of secretory cells, the formation of SNARE complexes is a major event preceding membrane fusion and mediator release (13,14). A range of SNARE proteins has been identified in neutrophils, and there is much evidence that indicates their implication in the regulation of granule fusion (13,(15)(16)(17)(18)(19). Munc13 proteins constitute a family of four mammalian homologs of Caenorhabditis elegans Unc-13.…”

Section: Munc13-4 Regulates Granule Secretion In Human Neutrophilsmentioning

confidence: 99%

Munc13-4 Regulates Granule Secretion in Human Neutrophils

Pivôt-Pajot

Varoqueaux

Basile

et al. 2008

The Journal of Immunology

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The neutrophil plays a central role in the innate host immune defense. Regulated exocytosis of its granules and release of antimicrobial and cytotoxic substances are key events to limit the spread of pathogens. However, the molecular mechanisms that control exocytosis of neutrophil granules are ill-defined. Recently, it was shown that Munc13-4 is essential for the priming of granules in several hematopoietic cells. In this study, we show that Munc13-4 is expressed in human neutrophils, and that its expression is increased during granulocytic differentiation of HL-60 and PLB-985 cells. Cell fractionation analysis reveals that Munc13-4 is mainly cytosolic and is recruited rapidly to membranes following stimulation with fMLF (N-formyl-methionyl-leucyl-phenylalanine). Moreover, a pool of Munc13-4 associated with mobilizable secondary and tertiary granules is relocalized to the plasma membrane after stimulation with fMLF. The fMLF-induced translocation of Munc13-4 is strictly dependent on calcium in neutrophils. C2 domains of Munc13-4 are essential for binding to phospholipid vesicles in a Ca2+-independent manner. Finally, down-regulation of Munc13-4 using small interfering RNA decreases exocytosis of tertiary granules in PLB-985 cells, whereas overexpression of Munc13-4 enhances secretion of MMP-9 (matrix metalloproteinase-9) from tertiary granules. Our findings suggest a role for Munc13-4 as a component of the secretory machinery in neutrophils.

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Combinatorial SNARE Complexes Modulate the Secretion of Cytoplasmic Granules in Human Neutrophils

Cited by 104 publications

References 63 publications

Chloride Movements in Human Neutrophils during Phagocytosis: Characterization and Relationship to Granule Release

Chloride Movements in Human Neutrophils during Phagocytosis: Characterization and Relationship to Granule Release

Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms

Munc13-4 Regulates Granule Secretion in Human Neutrophils

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